Asymmetric opening and closing prosthetic valve leaflet

ABSTRACT

Described embodiments are directed toward prosthetic valves having leaflets that move asymmetrically in that a leaflet second side region of the leaflet initially moves toward the open position before a leaflet first side region and the leaflet first side region initially moves toward the closed position before the leaflet second side region. In the fully open position, the leaflet first side region opens less than the leaflet second side region. Asymmetric opening and final open position, in synchrony with the other leaflets having the same motion and final open position creates spiral flow exiting the open valve that increases blood flow on the downstream side of the leaflet and thus reduces stagnation of the blood that might lead to thrombus formation. Controlled asymmetric movement of the leaflet reduces closing volume by initiating closure on the leaflet first side region and finishing closures on the leaflet second side region.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a Division of U.S. application Ser. No. 14/561,148,filed Dec. 4, 2014, entitled ASYMMETRIC OPENING AND CLOSING PROSTHETICVALVE LEAFLET, which claims priority to U.S. Provisional ApplicationSer. No. 61/974,653, filed Apr. 3, 2014, entitled ASYMMETRIC OPENING ANDCLOSING PROSTHETIC VALVE LEAFLET, and 61/913,235, filed Dec. 6, 2013,entitled ASYMMETRIC OPENING AND CLOSING PROSTHETIC VALVE LEAFLET, all ofwhich are herein incorporated by reference in their entireties.

FIELD

The present disclosure relates generally to prosthetic valves and morespecifically, synthetic flexible leaflet-type prosthetic valve devicesand methods.

BACKGROUND

Bioprosthetic valves have been developed that attempt to mimic thefunction and performance of a native valve. Flexible leaflets arefabricated from biological tissue such as bovine pericardium. In somevalve designs the biological tissue is sewn onto a relatively rigidframe that supports the leaflets and provides dimensional stability whenimplanted. Although bioprosthetic valves can provide excellenthemodynamic and biomechanical performance in the short term, they areprone to calcification and cusp tears, among other failure modes,requiring reoperation and replacement.

Attempts have been made to use synthetic materials, such aspolyurethane, among others, as a substitute for the biological tissue,to provide a more durable flexible leaflet prosthetic valve, hereinreferred to as a synthetic leaflet valve (SLV). However, syntheticleaflet valves have not become a valid valve replacement option sincethey suffer premature failure, due to, among other things, suboptimaldesign and lack of a durable synthetic material.

The leaflets move under the influence of fluid pressure. In operation,the leaflets open when the upstream fluid pressure exceeds thedownstream fluid pressure and close when the downstream fluid pressureexceeds the upstream fluid pressure. The free edges of the leafletscoapt under the influence of downstream fluid pressure closing the valveto prevent downstream blood from flowing retrograde through the valve.

It has been found that in some very flexible leaflet prosthetic valves,the leaflets do not open and close in a controlled manner. Thedurability of the leaflets is largely controlled by the character ofbending exhibited by the leaflet during the opening-closing cycle. Smallradius bends, creases and particularly intersecting creases, can producehigh stress zones in the leaflet. These high stress zones can cause theformation of holes and tears under repetitive loading. If the leafletbending is unrestricted, not only do creases form, but creaseintersections lead to formation of large three dimensional structures(e.g., surface disruptions) that oppose bending and slow down theleaflet motion, both in opening and closing. This slow down of leafletmotion leads to an increase in closing volume; that is, the volume ofblood that travels back through the valve during the closing phase inorder to close the valve. It is advantageous to minimize closing volume.

Further, the flexible nature of the very flexible leaflet can createregions of blood pooling behind the leaflet when in the open positionpotentially causing blood clots to form at the leaflet base and near theattachment of the leaflet to the frame.

What is needed in the art is a flexible leaflet prosthetic valve thatprovides a more controlled leaflet movement that reduces closing volumeand potential for blood pooling behind the leaflet and near anyattachment of the leaflet to a support structure.

SUMMARY

Described embodiments are directed to flexible leaflet prosthetic heartvalves in which the leaflets move into the open and closed position in amore controlled manner. Each leaflet moves asymmetrically in that aleaflet second side region of the leaflet initially moves toward theopen position before a leaflet first side region and the leaflet firstside region initially moves toward the closed position before theleaflet second side region. Further, in the fully open position, theleaflet first side region opens less than the leaflet second sideregion. Such asymmetric opening and final open position, in synchronywith the other leaflets having the same motion and final open positioncreates spiral flow exiting the open valve that assists in creating anaxial vortex flow that increases blood flow on the downstream side ofthe leaflet and thus reduces stagnation of the blood that might lead tothrombus formation. Further, controlled asymmetric movement of theleaflet reduces closing volume by initiating closure on the leafletfirst side region and finishing closures on the leaflet second sideregion, reducing leaflet buckling resistance to closure by, in part,allowing one region of the leaflet to close before another region.Further, the leaflet open position is controlled such that fluid flowacross the leaflet first side region extends further into the valveorifice of the valve relative to the leaflet second side region tofurther expose the leaflet downstream side to the retrograde blood flowwhich increases washout of the blood from the leaflet downstream sideand exposes the leaflet downstream side to improved reverse blood flowand to assist closing during the closing phase.

Described embodiments are directed to flexible leaflet prosthetic valvesin which the leaflets have regions of increased stiffness relative toother regions of the leaflet, so as to provide asymmetric opening andclosing of the leaflet. The region of increased stiffness provides thatthe leaflet moves into the open and closed position in a more controlledmanner. Further, the region of increased stiffness positions the openleaflet so as to provide an increased blood flow behind the leaflet andwhere the leaflet attaches to the leaflet frame.

In accordance with an embodiment, a prosthetic valve comprises a leafletframe and a plurality of leaflets coupled to the leaflet frame. Eachleaflet has a free edge, a leaflet first side, a leaflet second side,and a leaflet base therebetween. The leaflet first side, leaflet secondside, and leaflet base are coupled to the leaflet frame. Each leaflethas a leaflet first side region adjacent the leaflet first side, aleaflet second side region adjacent the leaflet second side, and aleaflet central region therebetween and adjacent the leaflet base. Atleast a portion of the leaflet first side region has a stiffness that isgreater than the stiffness of the leaflet second side region and leafletcentral region.

In accordance with another embodiment, a prosthetic valve comprises aframe having a generally tubular shape with attached film. The framedefines a plurality of leaflet windows. Each leaflet window defines aleaflet window first side, a leaflet window second side, and a leafletwindow base. The leaflet window first side and the leaflet window secondside diverge from the leaflet window base. The film defines at least oneleaflet extending from each of the leaflet windows. Each leaflet has afree edge, a leaflet first side that is coupled to the leaflet windowfirst side, a leaflet second side that is coupled to the leaflet windowsecond side, and a leaflet base therebetween that is coupled to theleaflet window base. Each leaflet has a leaflet first side regionadjacent the leaflet first side and extending to a substantially axialline from the leaflet free edge to the intersection between the leafletwindow first side and the leaflet window base, a leaflet second regionadjacent the leaflet second side and extending to a substantially axialline from the leaflet free edge to the intersection between the leafletwindow second side and the leaflet window base, and a leaflet centralregion therebetween and adjacent the leaflet free edge to the leafletbase. At least a portion of the leaflet first side region has astiffness that is greater than the stiffness of the leaflet secondregion and leaflet central region.

In accordance with another embodiment, a prosthetic valve comprises aplurality of leaflets where each leaflet includes a leaflet first sideregion and a leaflet second side region opposite from the leaflet firstside region. The leaflet first side region has a thickness that isthicker than a thickness of the second side region.

In accordance with another embodiment, a prosthetic valve comprises aplurality of leaflets where each leaflet includes a leaflet first sideand a leaflet second side opposite from the leaflet first side. Eachleaflet first side is coupled with the leaflet second side of anadjacent leaflet at a commissure. The plurality of leaflets defines anorifice when the leaflets are in an open position. Each of the leafletfirst sides extends further into the orifice than each of the leafletsecond sides when the leaflets are in the open position.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings are included to provide a furtherunderstanding of the present disclosure and are incorporated in andconstitute a part of this specification, illustrate embodimentsdescribed herein, and together with the description serve to explain theprinciples discussed in this disclosure.

FIG. 1A is a side view of a prosthetic valve in accordance with anembodiment;

FIG. 1B is a perspective view of the embodiment of the valve of FIG. 1A;

FIG. 1C is an axial view of the embodiment of the valve of FIG. 1A in anopen configuration;

FIG. 1D is an axial view of the embodiment of the prosthetic valve ofFIG. 2A in a partially open or partially closed configuration;

FIG. 1E is an axial view of the embodiment of the prosthetic valve ofFIG. 2A in a closed configuration;

FIG. 2A is a representation of an embodiment of a leaflet frame unrolledto a flat orientation with a strain relief frame covering and leafletreinforcing member;

FIG. 2B is a representation of an embodiment of a leaflet frame unrolledto a flat orientation of FIG. 2A with a strain relief frame covering andleaflet reinforcing member, also with a leaflet;

FIG. 3A is a perspective view of another embodiment of a valve frame;

FIG. 3B is an axial view of the embodiment of the valve of FIG. 3A in anopen configuration;

FIG. 4A is a representation of an embodiment of a leaflet frame of theembodiment of FIG. 3A unrolled to a flat orientation with a strainrelief frame covering and leaflet reinforcing member;

FIG. 4B is a representation of an embodiment of a leaflet frame unrolledto a flat orientation of FIG. 3A with a strain relief frame covering andleaflet reinforcing member, also with a leaflet;

FIG. 5A is a side view of the leaflet frame on an assembly mandrel, inaccordance with an embodiment;

FIG. 5B is a side view of the leaflet frame on an assembly mandrel, inaccordance with an embodiment;

FIG. 5C is a side view of the leaflet frame construct showing the strainrelief frame covering and leaflet reinforcing member, in accordance withan embodiment;

FIG. 5D is a side view of the leaflet frame construct on an assemblymandrel overlaid with leaflet material, in accordance with anembodiment;

FIG. 6A is a side view of the leaflet frame on a mandrel, in accordancewith an embodiment; and

FIG. 6B is a perspective view of the leaflet frame on the mandrel ofFIG. 6A.

DETAILED DESCRIPTION

Persons skilled in the art will readily appreciate that various aspectsof the present disclosure can be realized by any number of methods andapparatus configured to perform the intended functions. Stateddifferently, other methods and apparatuses can be incorporated herein toperform the intended functions. It should also be noted that theaccompanying drawing figures referred to herein are not necessarilydrawn to scale, but may be exaggerated to illustrate various aspects ofthe present disclosure, and in that regard, the drawing figures shouldnot be construed as limiting.

Although the embodiments herein may be described in connection withvarious principles and beliefs, the described embodiments should not bebound by theory. For example, embodiments are described herein inconnection with prosthetic valves, more specifically cardiac prostheticvalves. However, embodiments within the scope of this disclosure can beapplied toward any valve or mechanism of similar structure and/orfunction. Furthermore, embodiments within the scope of this disclosurecan be applied in non-cardiac applications.

The term leaflet as used herein in the context of prosthetic valves is acomponent of a one-way valve wherein the leaflet is operable to movebetween an open and closed position under the influence of a pressuredifferential. In an open position, the leaflet allows blood to flowthrough the valve. In a closed position, the leaflet substantiallyblocks retrograde flow through the valve. In embodiments comprisingmultiple leaflets, each leaflet cooperates with at least one neighboringleaflet to block the retrograde flow of blood. The pressure differentialin the blood is caused, for example, by the contraction of a ventricleor atrium of the heart, such pressure differential typically resultingfrom a fluid pressure building up on one side of the leaflets whenclosed. As the pressure on an inflow side of the valve rises above thepressure on the outflow side of the valve, the leaflets opens and bloodflows therethrough. As blood flows through the valve into a neighboringchamber or blood vessel, the pressure on the inflow side equalizes withthe pressure on the outflow side. As the pressure on the outflow side ofthe valve rises above the blood pressure on the inflow side of thevalve, the leaflet returns to the closed position generally preventingretrograde flow of blood through the valve.

The term membrane as used herein refers to a sheet of materialcomprising a single composition, such as, but not limited to, expandedfluoropolymer.

The term composite material as used herein refers to a combination of amembrane, such as, but not limited to, expanded fluoropolymer, and anelastomer, such as, but not limited to, a fluoroelastomer. The elastomermay be imbibed within a porous structure of the membrane, coated on oneor both sides of the membrane, or a combination of coated on and imbibedwithin the membrane.

The term laminate as used herein refers to multiple layers of membrane,composite material, or other materials, such as elastomer, andcombinations thereof.

The term film as used herein generically refers to one or more of themembrane, composite material, or laminate.

The term biocompatible material as used herein generically refers to afilm or a biological material, such as, but not limited to, bovinepericardium.

The term leaflet window is defined as that space that a frame definesfrom which a leaflet extends. The leaflet may extend from frame elementsor adjacent to frame elements and spaced apart therefrom.

The terms native valve orifice and tissue orifice refer to an anatomicalstructure into which a prosthetic valve may be placed. Such anatomicalstructure includes, but is not limited to, a location wherein a cardiacvalve may or may not have been surgically removed. It is understood thatother anatomical structures that may receive a prosthetic valve include,but are not limited to, veins, arteries, ducts and shunts. Althoughreference is made herein to replacing a native valve with a prostheticvalve, it is understood and appreciated that a valve orifice or implantsite may also refer to a location in a synthetic or biological conduitthat may receive a valve for a particular purpose, and therefore thescope of the embodiments provided herein is not limited to valvereplacement.

As used herein, “couple” means to join, connect, attach, adhere, affix,or bond, whether directly or indirectly, and whether permanently ortemporarily.

Embodiments herein include various apparatus, systems, and methods for aprosthetic valve suitable for surgical and transcatheter placement, suchas, but not limited to, cardiac valve replacement. The valve is operableas a one-way valve wherein the valve defines a valve orifice into whichleaflets open to permit flow and close so as to occlude the valveorifice and prevent flow in response to differential fluid pressure.

Described embodiments are directed to flexible leaflet prosthetic valvesin which the leaflets move into the open and closed position in a morecontrolled manner. The leaflets move in synchrony with each other. Eachleaflet moves asymmetrically in that a leaflet second side region of theleaflet initially moves toward the open position before a leaflet firstside region and the leaflet first side region initially moves toward theclosed position before the leaflet second side region. Further, in thefully open position, the leaflet first side opens less than the leafletsecond side. The leaflet first side region of one leaflet is adjacent tothe leaflet second side region of an adjacent leaflet. Such asymmetricopening and final open position, in synchrony with the other leafletshaving the same motion and final open position, creates spiral flowexiting the open valve that assists in creating an axial vortex flowthat increases blood flow on the downstream side of the leaflet and thusreduces stagnation of the blood that might lead to thrombus formation.Further, controlled asymmetric movement of the leaflet reduces closingvolume by initiating closure on the leaflet first side region andfinishing closures on the leaflet second side region, reducing leafletbuckling resistance to closure by, in part, allowing one side region ofthe leaflet to close before another side region. Further, the leafletopen position is controlled such that the leaflet first side regionextends further into the valve orifice of the valve relative to theleaflet second side region to further expose the leaflet downstream sideto the retrograde blood flow which increases washout of the blood fromthe leaflet downstream side and exposes the leaflet downstream side toimproved reverse blood flow and to assist closing during the closingphase.

In accordance with embodiments provided herein, at least a portion ofthe leaflet first side region is configured to be more resistant tomotion as compared with the leaflet second side region. The resistant tomotion may be affected in a number of ways, including, but not limitedto, configuring the bending modulus of the leaflet material to have ahigher bending modulus in the leaflet first side region as compared withthe leaflet second side region. The resistant to motion may be affectedin a number of ways, including, but not limited to, adding a reinforcingmember that is separate from but coupled to the leaflet first sideregion. The resistant to motion may be affected in a number of ways,including, but not limited to, increasing the number of layers of alaminated composite that makes up the leaflet, and thus the thickness inthe leaflet first side region as compared with the leaflet second sideregion.

Embodiments provided herein address controlled leaflet opening andclosing. Embodiments provided herein provide a feature of differingleaflet stiffness from one side region of the leaflet to the other sideregion. The less stiff side region of the leaflet will initiate openingbefore the stiffer side of the leaflet. Therefore, the leaflet will openasymmetrically with respect to the leaflet free edge rather thansymmetrically as with a leaflet having a uniform or symmetric stiffnessproperty. This asymmetric movement minimizes crease formation, which isof particular importance in thin, high-modulus leaflets. If the leafletbending is unrestricted, not only may creases form, but creaseintersections lead to formation of large three dimensional structures(e.g., surface disruptions) that oppose bending and slow down theleaflet motion, both in opening and closing. Embodiments provided hereincontrol leaflet opening and to minimize crease formation provided by thecontrolled asymmetric opening and closing of the leaflet.

Embodiments provided herein address blood pooling or stagnation that canlead to clot formation behind the leaflet and along the intersection ofthe leaflet and the frame when the leaflet is open. Embodiments providedherein provide a feature of differing leaflet stiffness from one sideregion of the leaflet to the other side region. The stiffer side regionof the leaflet will open to a lesser extent than the less stiff sideregion. Since the stiffer side region of the leaflet does not open fullyand therefore protrudes into the flow more so than the less stiff sideregion, retrograde blood flow may better extend behind the leaflet, thedownstream side, producing a washing effect along the attachment of theleaflet to the frame and, in particular, at the base of the leaflet onthe downstream side of the leaflet. Since the stiffer side region of theleaflet protrudes into the retrograde flow more so than the less stiffside region, when the flow reverses, the stiffer leaflet side regionprotruding into the flow will actuate the closing of the valve muchsooner and in a more controlled manner. Therefore, the leaflet willclose asymmetrically from the more stiff side region to the less stiffside region with respect to the leaflet free edge rather than randomlyand chaotically as with a very thin and flexible leaflet having auniform or symmetric stiffness property. This asymmetric movementminimizes crease formation and provides a faster closing response, whichis of particular importance in thin, high-modulus leaflets. Embodimentsprovided herein control leaflet closing that provides minimization ofcrease formation and a faster closing response provided by thecontrolled asymmetric closing of the leaflet.

Valve

FIG. 1A is a side view of a valve 100, in accordance with an embodiment.FIG. 1B is a perspective view of the valve 100 of FIG. 1A. FIGS. 1C, 1Dand 1E are axial views of the valve 100 of FIG. 1A in an open, partiallyopen, and closed configuration, respectively. The valve 100 comprises aleaflet frame 130 and film 160 that defines leaflets 140. In FIGS. 1A,1B and 1E, the leaflets 140 are shown slightly open to better show thefeatures but it is understood that a valve 100 that is fully closed willhave the leaflet free edges 142 of the leaflets 140 coming together tocoapt under the influence of downstream fluid pressure which results inclosing the valve 100 to prevent downstream blood from flowingretrograde through the valve 100.

Frame

Referring to FIGS. 1A-1E, the leaflet frame 130 is a generally tubularmember, in accordance with an embodiment. The leaflet frame 130comprises a leaflet frame first end 121 a and a frame second end 121 bopposite the leaflet frame first end 121 a. The leaflet frame 130comprises a leaflet frame outer surface 126 a and a leaflet frame innersurface 126 b opposite the leaflet frame outer surface 126 a, as shownin FIG. 1A. The leaflet frame 130 defines commissure posts 136 thatcouple to the leaflet free edges 142. The commissure posts 136 aredefined by a vertical element 122.

FIGS. 2A and 2B are side views of a leaflet frame 130 of a valve 100wherein the leaflet frame 130 has been longitudinally cut and laid opento better illustrate the elements of the generally tubular-shapedleaflet frame 130, in accordance with an embodiment. In FIG. 2A, aleaflet reinforcing member 149 is shown in dashed line to representwhere the leaflet reinforcing member 149 is located within the leafletwindow 137, the leaflet window 137 being defined by the leaflet windowfirst side 133 a and the leaflet window second side 133 b, and theleaflet window base 134. The leaflet reinforcing member 149 is coupledto the leaflet window first side 133 a and extends into what will be theleaflet first side region 184 a, as shown in FIG. 2B. Also in FIG. 2A,an optional strain relief frame covering 152 is shown in dashed linefollowing the contour of the leaflet window 137. The strain relief framecovering 152 is a covering of film 160 that covers the leaflet frame 130and extends about 0.5 mm to 1.0 mm into the leaflet window 137. Thestrain relief frame covering 152 provides a transition region thatprovides strain relief between the leaflet frame 130 and the leaflet140.

In FIG. 2B, a leaflet 140 is shown in solid line to represent where theleaflet 140 is located within the leaflet window 137 and the leafletreinforcing member 149, shown in dashed line, being within the leafletfirst side region 184 a.

The leaflet frame 130 may comprise a cut tube, or any other elementsuitable for the particular purpose. The leaflet frame 130 may beetched, cut, laser cut, or stamped into a tube or a sheet of material,with the sheet then formed into a substantially cylindrical structure.

The leaflet frame 130 can comprise any metallic or polymeric materialthat is biocompatible. For example, the leaflet frame 130 can comprise amaterial, such as, but not limited to nitinol, cobalt-nickel alloy,stainless steel, or polypropylene, acetyl homopolymer, acetyl copolymer,ePTFE, other alloys or polymers, or any other biocompatible materialhaving adequate physical and mechanical properties to function asdescribed herein.

Referring to FIGS. 2A and 2B, the leaflet frame comprises a plurality ofspaced apart leaflet frame elements defining substantially an isoscelestrapezoid interconnected by a base element 138 defining leaflet windows137. Each of the leaflet window first side 133 a and leaflet windowsecond side 133 b is defined by a side of one trapezoid and a side of anadjacent trapezoid defining a trapezoidal shape, and wherein eachleaflet window base 134 is defined by the base element 138 between theleaflet window first side 133 a and leaflet window second side 133 b. Inthe embodiment of FIG. 1B there are three interconnected leaflet windows137, where a leaflet window first side 133 a of one leaflet window 137is interconnected with an adjacent leaflet window second side 133 b ofan adjacent leaflet window 137.

Referring again to FIGS. 1A, 2A and 2B, the leaflet frame first end 121a further comprises commissure posts 136 extending from an apex of theleaflet frame elements defining substantially an isosceles trapezoid.The commissure post 136 may affect the leaflet free edge 142 so as tocreate a larger or wider coaptation region 146 between adjacent leafletfree edges 142.

In accordance with an embodiment, the leaflet frame 130 comprises aframe having a shape determined, at least in part, by wrapping a twodimensional isosceles trapezoid every 120 degrees onto the tubular shapeof the leaflet frame 130, the isosceles trapezoid having a leafletwindow base 134, a leaflet window first side 133 a, and a leaflet windowsecond side 133 b that diverge from the leaflet window base 134, andwherein a leaflet window first side 133 a and leaflet window second side133 b from adjacent isosceles trapezoids meet at the leaflet frame firstend 121 a and frame second end 121 b, as shown in FIG. 2A. A leaflet 140is shown located within the leaflet window 137, the leaflet window 137being defined by the leaflet window first side 133 a, the leaflet windowsecond side 133 b, and the leaflet window base 134.

In accordance with an embodiment of a valve 100, each leaflet 140 hassubstantially the shape of an isosceles trapezoid having a leaflet firstside 141 a and a leaflet second side 141 b, a leaflet base 143 and aleaflet free edge 142 opposite the leaflet base 143, wherein the leafletfirst side 141 a and a leaflet second side 141 b diverge from theleaflet base 143, wherein the leaflet base 143 is substantially flat, asshown in dashed lines in FIG. 2B.

FIG. 3 is a perspective view of a leaflet frame 230 that is a generallytubular member, in accordance with another embodiment. The leaflet frame230 comprises a frame first end 221 a and a frame second end 221 bopposite the frame first end 221 a. The leaflet frame 230 comprises aleaflet frame outer surface 226 a and a leaflet frame inner surface 226b opposite the leaflet frame outer surface 226 a, as shown in FIG. 3A.The leaflet frame 230 defines commissure posts 236 that couple to theleaflet free edges 242.

FIGS. 4A and 4B are side views of a leaflet frame 230 of a valve 200wherein the leaflet frame 230 has been longitudinally cut and laid opento better illustrate the elements of the generally tubular-shapedleaflet frame 230, in accordance with an embodiment. The leaflet framecomprises a plurality of interconnected parabolic leaflet frame elements235 terminating at commissure posts 236 defining leaflet windows 237.Each parabolic leaflet frame elements 235 may be defined by a leafletwindow first side 233 a and leaflet window second side 233 b on eitherside of a plane P symmetrically bisecting the parabolic leaflet frameelements 235 aligned with the axial axis X, shown in FIG. 3B.

The commissure posts 236 extend from an apex of intersecting parabolicleaflet frame elements 235. The length of the commissure post 236 maydefine the length of the coaptation region 146 between adjacent leafletfree edges 142. Where the commissure post 236 is made longer and theleaflet is attached thereto, a larger or wider coaptation region 146 maybe defined between adjacent leaflet free edges 142.

In accordance with an embodiment of a valve 200, each leaflet 240 hassubstantially the shape of a parabola having a leaflet first side 241 aincluding a leaflet first side region 284 a and a leaflet second side241 b including a leaflet second side region 284 b defined by a plane Psymmetrically aligned with the axial axis X bisecting the parabola, anda leaflet free edge 142 between the leaflet first side 241 a and aleaflet second side 241 b.

In FIG. 4B, a leaflet reinforcing member 249 is shown in dashed line torepresent where the leaflet reinforcing member 249 is located within theleaflet window 237. The leaflet reinforcing member 249 is coupled to theleaflet window first side 233 a and extends into what will be at least aportion of the leaflet first side region 284 a. Also in FIG. 4B, anoptional strain relief frame covering 252 is shown in dashed linefollowing the contour of the leaflet window 237. The strain relief framecovering 252 is a covering of film 160 that covers the leaflet frame 130and extends about 0.5 mm to 1.0 mm into the leaflet window 237. Thestrain relief frame covering 252 provides a transition region thatprovides strain relief between the leaflet frame 130 and the leaflet240. In FIG. 14B, a leaflet 240 is shown located within the leafletwindow 237 and the leaflet reinforcing member 249 being within theleaflet first side region 284 a.

Film

The film 160, as shown in FIG. 1A, is generally any sheet-like materialthat is biologically compatible and configured to couple to the leafletframe 130, in accordance with embodiments. It is understood that theterm “film” is used generically for one or more biocompatible materialssuitable for a particular purpose. The leaflets 140 are also comprisedof the film 160.

In accordance with an embodiment, the biocompatible material is a film160 that is not of a biological source and that is sufficiently flexibleand strong for the particular purpose, such as a biocompatible polymer.In an embodiment, the film 160 comprises a biocompatible polymer that iscombined with an elastomer, referred to as a composite.

Details of various types of film 160 are discussed below. In anembodiment, the film 160 may be formed from a generally tubular materialto at least partially cover the leaflet frame 130. The film 160 cancomprise one or more of a membrane, composite material, or laminate.Details of various types of film 160 are discussed below.

In an embodiment, the film 160 comprises a biocompatible polymer that iscombined with an elastomer, referred to as a composite material. Amaterial according to one embodiment includes a composite materialcomprising an expanded fluoropolymer membrane, which comprises aplurality of spaces within a matrix of fibrils, and an elastomericmaterial. It should be appreciated that multiple types of fluoropolymermembranes and multiple types of elastomeric materials can be combined toform a laminate while remaining within the scope of the presentdisclosure. It should also be appreciated that the elastomeric materialcan include multiple elastomers, multiple types of non-elastomericcomponents, such as inorganic fillers, therapeutic agents, radiopaquemarkers, and the like while remaining within the scope of the presentdisclosure.

In accordance with an embodiment, the composite material includes anexpanded fluoropolymer material made from porous ePTFE membrane, forinstance as generally described in U.S. Pat. No. 7,306,729 to Bacino.

The expandable fluoropolymer, used to form the expanded fluoropolymermaterial described, may comprise PTFE homopolymer. In alternativeembodiments, blends of PTFE, expandable modified PTFE and/or expandedcopolymers of PTFE may be used. Non-limiting examples of suitablefluoropolymer materials are described in, for example, U.S. Pat. No.5,708,044, to Branca, U.S. Pat. No. 6,541,589, to Baillie, U.S. Pat. No.7,531,611, to Sabol et al., U.S. patent application Ser. No. 11/906,877,to Ford, and U.S. patent application Ser. No. 12/410,050, to Xu et al.

The expanded fluoropolymer membrane can comprise any suitablemicrostructure for achieving the desired leaflet performance. Inaccordance with an embodiment, the expanded fluoropolymer comprises amicrostructure of nodes interconnected by fibrils, such as described inU.S. Pat. No. 3,953,566 to Gore. The fibrils radially extend from thenodes in a plurality of directions, and the membrane has a generallyhomogeneous structure. Membranes having this microstructure maytypically exhibit a ratio of matrix tensile strength in two orthogonaldirections of less than or equal to 2, and possibly less than 1.5.

In another embodiment, the expanded fluoropolymer membrane has amicrostructure of substantially only fibrils, as is generally taught byU.S. Pat. No. 7,306,729, to Bacino. The expanded fluoropolymer membranehaving substantially only fibrils, can possess a high surface area, suchas greater than 20 m²/g, or greater than 25 m²/g, and in someembodiments can provide a highly balanced strength material having aproduct of matrix tensile strengths in two orthogonal directions of atleast 1.5×10⁵ MPa², and/or a ratio of matrix tensile strengths in twoorthogonal directions of less than 4, and possibly less than 1.5.

The expanded fluoropolymer membrane can be tailored to have any suitablethickness and mass to achieve the desired leaflet performance. By way ofexample, but not limited thereto, the leaflet 140 comprises an expandedfluoropolymer membrane having a thickness of about 0.1 μm. The expandedfluoropolymer membrane can possess a mass per area of about 1.15 g/m².Membranes according to an embodiment of the invention can have matrixtensile strengths of about 411 MPa in the longitudinal direction and 315MPa in the transverse direction.

Additional materials may be incorporated into the pores or within thematerial of the membranes or in between layers of membranes to enhancedesired properties of the leaflet. Composite materials described hereincan be tailored to have any suitable thickness and mass to achieve thedesired leaflet performance. Composite materials according toembodiments can include fluoropolymer membranes and have a thickness ofabout 1.9 μm and a mass per area of about 4.1 g/m². In otherembodiments, the fluoropolymer membranes have a thickness of about 100μm and a mass per area of about 100 g/m².

The expanded fluoropolymer membrane combined with elastomer to form acomposite material provides the elements of the present disclosure withthe performance attributes required for use in high-cycle flexuralimplant applications, such as heart valve leaflets, in various ways. Forexample, the addition of the elastomer can improve the fatigueperformance of the leaflet by eliminating or reducing the stiffeningobserved with ePTFE-only materials. In addition, it may reduce thelikelihood that the material will undergo permanent set deformation,such as wrinkling or creasing, that could result in compromisedperformance. In one embodiment, the elastomer occupies substantially allof the pore volume or space within the porous structure of the expandedfluoropolymer membrane. In another embodiment the elastomer is presentin a portion of the pores of the at least one fluoropolymer layer.Having elastomer filling the pore volume or present in a portion of thepores reduces the space in which foreign materials can be undesirablyincorporated into the composite material. An example of such foreignmaterial is calcium that may be drawn into the membrane from contactwith the blood. If calcium becomes incorporated into the compositematerial, as used in a heart valve leaflet, for example, mechanicaldamage can occur during cycling open and closed, thus leading to theformation of holes in the leaflet and degradation in hemodynamics.

In an embodiment, the elastomer that is combined with the ePTFE is athermoplastic copolymer of tetrafluoroethylene (TFE) and perfluoromethylvinyl ether (PMVE), such as described in U.S. Pat. No. 7,462,675 toChang et al. As discussed above, the elastomer is combined with theexpanded fluoropolymer membrane such that the elastomer occupiessubstantially all of the void space or pores within the expandedfluoropolymer membrane to form a composite material. This filling of thepores of the expanded fluoropolymer membrane with elastomer can beperformed by a variety of methods. In one embodiment, a method offilling the pores of the expanded fluoropolymer membrane includes thesteps of dissolving the elastomer in a solvent suitable to create asolution with a viscosity and surface tension that is appropriate topartially or fully flow into the pores of the expanded fluoropolymermembrane and allow the solvent to evaporate, leaving the filler behind.

In one embodiment, the composite material comprises three layers: twoouter layers of ePTFE and an inner layer of a fluoroelastomer disposedtherebetween. Additional fluoroelastomers can be suitable and aredescribed in U.S. Publication No. 2004/0024448 to Chang et al.

In another embodiment, a method of filling the pores of the expandedfluoropolymer membrane includes the steps of delivering the filler via adispersion to partially or fully fill the pores of the expandedfluoropolymer membrane.

In another embodiment, a method of filling the pores of the expandedfluoropolymer membrane includes the steps of bringing the porousexpanded fluoropolymer membrane into contact with a sheet of theelastomer under conditions of heat and/or pressure that allow elastomerto flow into the pores of the expanded fluoropolymer membrane.

In another embodiment, a method of filling the pores of the expandedfluoropolymer membrane includes the steps of polymerizing the elastomerwithin the pores of the expanded fluoropolymer membrane by first fillingthe pores with a prepolymer of the elastomer and then at least partiallycuring the elastomer.

After reaching a minimum percent by weight of elastomer, the leafletsconstructed from fluoropolymer materials or ePTFE generally performedbetter with increasing percentages of elastomer resulting insignificantly increased cycle lives. In one embodiment, the elastomercombined with the ePTFE is a thermoplastic copolymer oftetrafluoroethylene and perfluoromethyl vinyl ether, such as describedin U.S. Pat. No. 7,462,675 to Chang et al., and other references thatwould be known to those of skill in the art. Other biocompatiblepolymers which can be suitable for use in leaflet 140 include but arenot limited to the groups of urethanes, silicones (organopolysiloxanes),copolymers of silicon-urethane, styrene/isobutylene copolymers,polyisobutylene, polyethylene-co-poly(vinyl acetate), polyestercopolymers, nylon copolymers, fluorinated hydrocarbon polymers andcopolymers or mixtures of each of the foregoing.

Leaflet

Each leaflet window 137 is provided with a biocompatible material, suchas a film 160, which is coupled to a portion of the leaflet window sides133 with the film 160 defining a leaflet 140, as shown in FIGS. 1A-1Dand 2B. Each leaflet 140 defines a leaflet free edge 142 and a leafletbase 143, in accordance with an embodiment. As will be described below,it is anticipated that a plurality of embodiments of leaflet shapes,including with and without a defined leaflet base 143, may be provided.In accordance with an embodiment, the film 160 is coupled to at least aportion of the leaflet window first side 133 a and leaflet window secondside 133 b and to the leaflet window base 134 where the leaflet 140 isdefined by the portion of the leaflet window first side 133 a, theleaflet window second side 133 b and to the leaflet window base 134. Theleaflet 140 has a leaflet upstream side 193 and a leaflet downstreamside 191 opposite the leaflet upstream side 193. The leaflet upstreamside 193 is that side of the leaflet 140 that is facing away from theleaflet frame 130 when in the open position and the leaflet downstreamside 191 is that side of the leaflet 140 that is facing toward theleaflet frame 130 when in the open position.

When the leaflets 140 are in a fully open position, the valve 100presents a substantially circular valve orifice 102 as shown in FIG. 1C.Fluid flow is permitted through the valve orifice 102 when the leaflets140 are in the open position. Since the leaflet first side region 184 ais stiffer than the leaflet second side region 184 b, the leaflet firstside region 184 a does not open fully leaving a pocket 194 defined inpart by the leaflet downstream side 191 adjacent the leaflet first sideregion 184 a. As the blood exits the valve 100, retrograde flow mayenter the pocket 194 so as to wash out the area defined by the leafletdownstream side 191.

A geometric orifice area (GOA), as is known in the art, is an areameasurement of an axial projection of an open area defined by the valvewhen in the fully open position. As explained below, a first portion ofa leaflet will extend further into the valve orifice defined by thevalve frame, that is, not open as much, than a second portion of thesame leaflet, which opens further. From an axial viewpoint, the firstportion of the leaflet will create a smaller GOA than the second portionof the leaflet

FIG. 1C is an axial view of the valve 100 in the fully open position. Asshown in FIG. 1C, the leaflets 140 do not completely open to conform tothe leaflet frame inner surface 126 b, therefore projecting a smallergeometric orifice area compared with an orifice area of a frame withoutleaflets. The leaflet frame inner surface 126 b in cross-sectiontransverse to the X axis defines a frame orifice 139 having a frameorifice area that is circular in shape.

The axial view shown in FIG. 1C is bisected into six segments by threeplanes P1, P2, P3 where each plane passes through one commissure post136, the axis X and bisects a leaflet 140 in half, defining a firstsegment 172 and a second segment 174. The leaflet first side region 184a of the leaflet 140 in the first segment 172 extends more into theframe orifice 139 defined by the leaflet frame inner surface 126 bdefining a smaller GOA, for example, up to 70 percent smaller, than theleaflet second side region 184 b in the second segment 174. The benefitof this relationship of the leaflet first side region 184 a extendinginto the valve orifice as compared to the leaflet second side region 184b will be detailed below.

FIG. 1D is an axial view of the valve 100 in the partially open positionor a partially closed position. The leaflet first side region 184 a ofone leaflet 140 is adjacent to the leaflet second side region 184 b ofan adjacent leaflet 140. The leaflet first side region 184 a is stiffercompared to the leaflet second side region 184 b. The leaflet secondside region 184 b will initially open first and will close last comparedto the leaflet first side region 184 a. This controlled motion providesa consistent leaflet motion from cycle to cycle imparting the benefitspreviously described.

As the leaflets 140 cycle between the open and closed positions, theleaflets 140 generally flex about the leaflet base 143 and the portionof the leaflet window first side 133 a and the leaflet window secondside 133 b to which the leaflets 140 are coupled. Since the leafletfirst side region 184 a is more stiff than the leaflet second sideregion 184 b, the leaflet first side 141 a does not flex as much aboutthe leaflet window first side 133 a as compared with the leaflet secondside 141 b defining a channel 145 between the leaflet first side 141 aof one leaflet 140 and the leaflet second side 141 b of an adjacentleaflet 140 when the leaflet is not in the closed position. The channel145 is defined when the leaflet 140 moves from the closed position. Thechannel 145 allows for blood flow therethrough throughout the openingphase of the leaflet 140 and thus reduces the potential for bloodpooling, stagnation and clot formation between the leaflet first side141 a and the leaflet window first side 133 a, and the leaflet secondside 141 b and the leaflet window second side 133 b, and therebetween.

When the valve 100 is closed, generally about half of each leaflet freeedge 142 abuts an adjacent half of a leaflet free edge 142 of anadjacent leaflet 140, as shown in FIG. 1E. The three leaflets 140 of theembodiment of FIG. 1E meet at a triple point 148. The valve orifice 102is occluded when the leaflets 140 are in the closed position stoppingfluid flow. Although the leaflet first side region 184 a is stiffer thanthe leaflet central region 182 and the leaflet second side region 184 b,the flexibility of the leaflet central region 182 and the leaflet secondside region 184 b of an adjacent leaflet 140 allows for coaptation withthe leaflet first side region 184 a allowing for proper closing of thevalve 100.

Referring to FIG. 1E, in accordance with an embodiment, each leaflet 140includes a leaflet central region 182, a leaflet first side region 184a, and a leaflet second side region 184 b on opposite sides of theleaflet central region 182. The leaflet central region 182 is defined bya shape substantially that of a rectangle defined by two leaflet centralregion sides 183, the leaflet base 143 and the leaflet free edge 142.The two leaflet central region sides 183 extend from the leaflet base143 to the leaflet free edge 142.

In accordance with an embodiment, the leaflet first side region 184 a isstiffer than the leaflet central region 182 and the leaflet second sideregion 184 b. The stiffness characteristics of the leaflet first sideregion 184 a, leaflet second side region 184 b and the leaflet centralregion 182 may be affected by any suitable means. In accordance with anembodiment, the leaflet 140 comprises a film that is a laminate ofmultiple layers of composite material. Additional layers of compositematerial are provided in the leaflet first side region 184 a whichimparts additional stiffness to the leaflet first side region 184 a ascompared with the leaflet central region 182 and the leaflet second sideregion 184 b. Example 1 provides additional details as to the embodimentjust described.

Referring to the embodiment of FIGS. 3A, 3B and 4A, 4B, in contrast tothe embodiment of FIGS. 1B, 2A and 2B, the parabolic shaped leafletwindow 237 does not define a distinct base but only a leaflet windowfirst side 233 a and leaflet window second side 233 b on either side ofa plane P symmetrically bisecting the parabolic leaflet frame elements235 aligned with the axial axis X, shown in FIGS. 4A and 4B. Therefore,the film 160 is coupled to at least a portion of the leaflet windowfirst side 233 a and leaflet window second side 233 b where the leaflet240 is defined by the portion of the leaflet window first side 233 a andthe leaflet window second side 133 b. The leaflet 240 has a leafletupstream side 193 and a leaflet downstream side 191 opposite the leafletupstream side 193. The leaflet upstream side 193 is that side of theleaflet 140 that is facing away from the leaflet frame 230 when in theopen position and the leaflet downstream side 191 is that side of theleaflet 240 that is facing toward the leaflet frame 130 when in the openposition.

The embodiments of FIGS. 1A-E and 3, 4A and 4B are examples of twodifferent leaflet and leaflet window geometries that are suitable forthe particular purpose. It is understood that other leaflet and leafletwindow geometries may also be suitable for the particular purpose andare not limited thereto.

The axial view of the valve 200 shown in FIG. 3B is bisected into sixsegments by three planes P1, P2, P3 where each plane passes through onecommissure post 236, the axis X and bisects a leaflet 240 in half,defining a first segment 172 and a second segment 174. The portion ofthe leaflet in the first segment 172 defines a smaller GOA than theportion of the leaflet in the second segment 174, by virtue of theleaflet first side region 284 a extending further into the frame orifice139 defined by the leaflet frame inner surface 126 b.

FIG. 3B is an axial view of the valve 200 in the partially open positionor a partially closed position. The leaflet first side region 284 a ofone leaflet 240 is adjacent to the leaflet second side region 284 b ofan adjacent leaflet 240. The leaflet first side region 284 a is stiffercompared to the leaflet second side region 284 b. The leaflet secondside region 284 b will initially open first and will close last comparedto the leaflet first side region 284 a. This controlled motion providesa consistent leaflet motion from cycle to cycle imparting the benefitspreviously described.

The leaflet 140 can be configured to actuate at a pressure differentialin the blood caused, for example, by the contraction of a ventricle oratrium of the heart, such pressure differential typically resulting froma fluid pressure building up on one side of the valve 100 when closed.As the pressure on an inflow side of the valve 100 rises above thepressure on the outflow side of the valve 100, the leaflet 140 opens andblood flows therethrough. As blood flows through the valve 100 into aneighboring chamber or blood vessel, the pressure equalizes. As thepressure on the outflow side of the valve 100 rises above the bloodpressure on the inflow side of the valve 100, the leaflet 140 returns tothe closed position generally preventing the retrograde flow of bloodthrough the inflow side of the valve 100.

It is understood that the leaflet frame 130 may comprise any number ofleaflet windows 137, and thus leaflets 140, suitable for a particularpurpose, in accordance with embodiments. Leaflet frames 130 comprisingone, two, three or more leaflet windows 137 and corresponding leaflets140 are anticipated.

Although embodiments provided above comprise a leaflet frame thatsupports the leaflets, it is understood and appreciated that theleaflets may not necessarily be supported by a frame. In accordance withan embodiment, the leaflets may be supported by the inner wall within asolid-walled conduit without a frame that defines leaflet windows andcommissure posts. In other embodiments, the leaflets may be constructedas in the tissue valve art that are formed into the desired shapewithout a frame.

In another embodiment of a valve including a plurality of leaflets, eachleaflet includes a leaflet first side and a leaflet second side oppositefrom the leaflet first side. Each leaflet first side is coupled with theleaflet second side of an adjacent leaflet at a commissure. Theplurality of leaflets defines an orifice, also referred to as a lumen,when the leaflets are in an open position. Each of the leaflet firstsides extend further into the orifice than each of the leaflet secondsides.

In another embodiment, a prosthetic valve comprises a plurality ofleaflets. Each leaflet includes a leaflet first side region and aleaflet second side region opposite from the leaflet first side region.Each leaflet defines a leaflet base and a leaflet free edge oppositefrom the leaflet base. Each leaflet first side region is coupled withthe leaflet second side region of an adjacent leaflet at a commissure.The leaflet base of the plurality of leaflets defines an orifice. Theleaflet second side regions extend further into the orifice than theleaflet first side region when the leaflets are in the fully openposition.

In another embodiment, a prosthetic valve comprises a plurality ofleaflets. Each leaflet includes a leaflet first side region and aleaflet second side region opposite from the leaflet first side region.At least a first portion of the leaflet first side region has a firstthickness and the leaflet second side region has a second thicknesswherein the first thickness is greater than the second thickness. Inoperation, each leaflet opens asymmetrically. In one embodiment, thefirst thickness may be ten times greater than the second thickness.

In another embodiment, a prosthetic valve comprises a plurality ofleaflets. Each leaflet includes a leaflet first side region and aleaflet second side region opposite from the leaflet first side region.The leaflet first side region has a first bending stiffness and theleaflet second side region has a second bending stiffness. The firstbending stiffness is greater than the second bending stiffness. Inoperation, each leaflet opens asymmetrically.

In another embodiment, a prosthetic valve comprises a plurality ofleaflets. Each leaflet includes a leaflet first side region and aleaflet second side region opposite from the leaflet first side region.The leaflet first side region being more resistant to moving comparedwith the leaflet second side region. In operation, each leaflet opensasymmetrically.

In another embodiment, a prosthetic valve comprises a plurality ofleaflets. Each leaflet includes a leaflet first side region and aleaflet second side region opposite from the leaflet first side region.The leaflet first side region being slower to open compared with theleaflet second side region. In operation, each leaflet opensasymmetrically.

In another embodiment, a prosthetic valve comprises a plurality ofleaflets. Each leaflet includes a leaflet first side region and aleaflet second side region opposite from the leaflet first side region.Each leaflet defines a leaflet base and a leaflet free edge oppositefrom the leaflet base. Each leaflet first side region is coupled withthe leaflet second side region of an adjacent leaflet at a commissure.The leaflet base of the plurality of leaflets defines an orifice. Atleast one of the leaflet second side regions extends further into theorifice than the leaflet first side region when the leaflets are in thefully open position.

In another embodiment, a prosthetic valve comprises a plurality ofleaflets. At least one leaflet includes a leaflet first side region anda leaflet second side region opposite from the leaflet first sideregion. The leaflet first side region has a first thickness and theleaflet second side region has a second thickness. The first thicknessis greater than the second thickness.

In another embodiment, a prosthetic valve comprises a plurality ofleaflets. Each leaflet includes a leaflet first side region and aleaflet second side region opposite from the leaflet first side region.At least one of the leaflets has a leaflet first side region having afirst bending stiffness and the leaflet second side region having asecond bending stiffness, wherein the first bending stiffness is greaterthan the second bending stiffness.

In another embodiment, a prosthetic valve comprises a plurality ofleaflets. Each leaflet includes a leaflet first side region and aleaflet second side region opposite from the leaflet first side region.At least one of the leaflets presents with the leaflet first side regionbeing more resistant to moving compared with the leaflet second sideregion.

In another embodiment, a prosthetic valve comprises a plurality ofleaflets. Each leaflet includes a leaflet first side region and aleaflet second side region opposite from the leaflet first side region.At least one of the leaflets presenting the leaflet first side regionbeing slower to open compared with the leaflet second side region.

In another embodiment, a prosthetic valve comprises a plurality ofleaflets. Each leaflet includes a leaflet first side region and aleaflet second side region opposite from the leaflet first side region.At least one leaflet has a thickness that tapers from the leaflet firstside region to the leaflet second side region.

In another embodiment, a prosthetic valve comprises a plurality ofleaflets. Each leaflet includes a leaflet first side region and aleaflet second side region opposite from the leaflet first side region.At least one leaflet has a thickness that varies from the leaflet firstside region to the leaflet second side region.

One skilled in the art will appreciate that the leaflet embodimentsprovided herein may be applied to any prosthetic valve design regardlessas to how the leaflets are supported to function as described.

Other Considerations

In accordance with an embodiment, the valve 100 can be configured toprevent interference with a heart conduction system by not covering abundle branch in the left ventricle when implanted, such as might beencountered with an aortic valve replacement procedure. For example, thevalve 100 can comprise a length of less than about 25 mm or less thanabout 18 mm. The valve 100 can also comprise an aspect ratio of lessthan one, wherein the ratio describes the relationship between thelength of the valve 100 to the expanded, functional diameter. However,the valve 100 can be constructed at any length and, more generally, anydesirable dimension.

Sewing Cuff

In accordance with a valve 100 suitable for surgical implantation, thevalve 100 further comprises a sewing cuff about a leaflet frame 130 inaccordance with an embodiment. The sewing cuff is operable to providestructure that receives suture for coupling to the implant site. Thesewing cuff may comprise any suitable material, such as, but not limitedto, double velour polyester. The sewing cuff may be locatedcircumferentially around a perimeter of the base of the leaflet frame130. Sewing cuffs are known in the art.

The valve 100 can further comprise a bio-active agent. Bio-active agentscan be coated onto a portion or the entirety of the film 160 forcontrolled release of the agents once the valve 100 is implanted. Thebio-active agents can include, but are not limited to, vasodilator,anti-coagulants, anti-platelet, anti-thrombogenic agents such as, butnot limited to, heparin. Other bio-active agents can also include, butare not limited to agents such as, for example,anti-proliferative/antimitotic agents including natural products such asvinca alkaloids (i.e. vinblastine, vincristine, and vinorelbine),paclitaxel, epidipodophyllotoxins (i.e. etoposide, teniposide),antibiotics (dactinomycin (actinomycin D) daunorubicin, doxorubicin andidarubicin), anthracyclines, mitoxantrone, bleomycins, plicamycin(mithramycin) and mitomycin, enzymes (L-asparaginase which systemicallymetabolizes L-asparagine and deprives cells which do not have thecapacity to synthesize their own asparagine); antiplatelet agents suchas G(GP) IIb/IIIa inhibitors and vitronectin receptor antagonists;anti-proliferative/antimitotic alkylating agents such as nitrogenmustards (mechlorethamine, cyclophosphamide and analogs, melphalan,chlorambucil), ethylenimines and methylmelamines (hexamethylmelamine andthiotepa), alkyl sulfonates-busulfan, nitrosoureas (carmustine (BCNU)and analogs, streptozocin), trazenes-dacarbazinine (DTIC);anti-proliferative/antimitotic antimetabolites such as folic acidanalogs (methotrexate), pyrimidine analogs (fluorouracil, floxuridine,and cytarabine), purine analogs and related inhibitors (mercaptopurine,thioguanine, pentostatin and 2-chlorodeoxyadenosine {cladribine});platinum coordination complexes (cisplatin, carboplatin), procarbazine,hydroxyurea, mitotane, aminoglutethimide; hormones (i.e. estrogen);anti-coagulants (heparin, synthetic heparin salts and other inhibitorsof thrombin); fibrinolytic agents (such as tissue plasminogen activator,streptokinase and urokinase), aspirin, dipyridamole, ticlopidine,clopidogrel, abciximab; antimigratory; antisecretory (breveldin);anti-inflammatory: such as adrenocortical steroids (cortisol, cortisone,fludrocortisone, prednisone, prednisolone, 6α-methylprednisolone,triamcinolone, betamethasone, and dexamethasone), non-steroidal agents(salicylic acid derivatives i.e. aspirin; para-aminophenol derivativesi.e. acetominophen; indole and indene acetic acids (indomethacin,sulindac, and etodalac), heteroaryl acetic acids (tolmetin, diclofenac,and ketorolac), arylpropionic acids (ibuprofen and derivatives),anthranilic acids (mefenamic acid, and meclofenamic acid), enolic acids(piroxicam, tenoxicam, phenylbutazone, and oxyphenthatrazone),nabumetone, gold compounds (auranofin, aurothioglucose, gold sodiumthiomalate); immunosuppressives: (cyclosporine, tacrolimus (FK-506),sirolimus (rapamycin), azathioprine, mycophenolate mofetil); angiogenicagents: vascular endothelial growth factor (VEGF), fibroblast growthfactor (FGF); angiotensin receptor blockers; nitric oxide donors;anti-sense oligionucleotides and combinations thereof; cell cycleinhibitors, mTOR inhibitors, and growth factor receptor signaltransduction kinase inhibitors; retenoids; cyclin/CDK inhibitors; HMGco-enzyme reductase inhibitors (statins); and protease inhibitors.

Method of Making

Embodiments described herein also pertain to a method of making thevalve 100 embodiments as described herein. In order to make the variousembodiments, a mandrel 710 that is cylindrical can be used. Withreference to FIGS. 3A-3C, the mandrel 710 comprises a structural formoperable to receive the leaflet frame 130 thereon.

An embodiment of a method of making a valve 100 comprises the steps ofwrapping a first film layer 160 a, e.g., a composite as describedherein, into a tubular form about the mandrel 710; placing the leafletframe 130 over the first film layer 160 a, as shown in FIG. 5A;thermally setting the assembly; trimming the first film layer 160 a todefine a leaflet reinforcing member 149 that is at least a portion ofthe leaflet first side region adjacent to and depending from the leafletwindow first side 133 a and removing the first film layer 160 a from theleaflet window that substantially defines the leaflet central region 182and the leaflet second side region 184 b; trimming the first film layer160 a to within about 0.5 to 1.0 mm of the leaflet window second side133 b and the leaflet window base 134 within the leaflet window 137, asshown in FIG. 5B; define at least a portion of the leaflet first sideregion and removing the first film layer 160 a from the leaflet windowthat substantially defines the leaflet central region 182 and theleaflet second side region 184 b, as shown in FIG. 5B; forming a secondfilm layer 160 b over the leaflet frame 130, as shown in FIG. 5C;thermally setting the assembly; receiving the assembly over a mandrel712 as shown in FIGS. 6A and 6B; cutting the film 160 across the leafletwindow top within the leaflet window 137.

The resulting valve 100 comprises a leaflet 140 having a leaflet firstside region 184 a that includes a leaflet reinforcing member 149 that isthe first film layer 160 a coupled to the second film layer 160 b, andthe leaflet central region 182 and leaflet second side region that onlyincludes the second film layer 160 b. A small border of the first filmlayer 160 a that depends from the leaflet window second side 133 b andthe leaflet window base 134 within the leaflet window 137 provides astrain relief that reduces the strain in the leaflet 140 at theinterface between the leaflet 140 and the leaflet window 137 of theleaflet frame 130.

Example

In an embodiment, a heart valve having polymeric leaflets formed from acomposite material having an expanded fluoropolymer membrane and anelastomeric material and joined to a metallic frame, and further ahaving a strain relief frame covering and a leaflet reinforcing memberwas constructed according to the following process:

A leaflet frame 130 was laser machined from a length of MP35N cobaltchromium tube hard tempered with an outside diameter of 23.0 mm and awall thickness of 0.6 mm. The leaflet frame was electro-polishedresulting in 0.01 mm material removal from each surface and leaving theedges rounded. The leaflet frame was cleaned by submersion in anultrasonic bath of acetone for approximately five minutes.

A strain relief was attached to the leaflet frame in the followingmanner. A steel metal mandrel having tapered diameter of 21.5 mm to 22.0mm outer diameter (taper angle of 0.1 degrees) was obtained. Athin-walled (122 μm) sintered 15 mm diameter ePTFE tube was disposed onthe metal mandrel by stretching radially over another tapered mandreland transferring to the 21.5 mm to 22.0 mm mandrel. One layer of asubstantially nonporous ePTFE membrane with an FEP coating wascircumferentially wrapped on the mandrel with the FEP side towards themandrel. This membrane was adhered by tacking using a soldering iron(Weller) set to 400° C., thereby creating a covered mandrel. The ePTFEand substantially nonporous ePTFE membrane combined to serve as an innerrelease liner. This entire release liner was removed in a later step.

A composite material comprising a membrane of ePTFE imbibed with afluoroelastomer was obtained. The composite material was comprised ofthree layers: two outer layers of ePTFE and an inner layer of afluoroelastomer disposed therebetween. The ePTFE membrane wasmanufactured according to the general teachings described in U.S. Pat.No. 7,306,729. The fluoroelastomer was formulated according to thegeneral teachings described in U.S. Pat. No. 7,462,675.

The ePTFE membrane had the following properties: thickness=about 15 μm;MTS in the highest strength direction=about 400 MPa; MTS strength in theorthogonal direction=about 250 MPa; Density=about 0.34 g/cm³; IBP=about660 KPa.

The fluoroelastomer consists essentially of between about 65 and 70weight percent perfluoromethyl vinyl ether and complementally about 35and 30 weight percent tetrafluoroethylene.

The percent weight of the fluoroelastomer relative to the ePTFE wasabout 53%.

The multi-layered composite had the following properties: thickness ofabout 40 μm; density of about 1.2 g/cm³; force to break/width in thehighest strength direction=about 0.953 kg/cm; tensile strength in thehighest strength direction=about 23.5 MPa (3,400 psi); force tobreak/width in the orthogonal direction=about 0.87 kg/cm; tensilestrength in the orthogonal direction=about 21.4 MPa (3100 psi), IPAbubble point greater than about 12.3 MPa, Gurley Number greater thanabout 1,800 seconds, and mass/area=about 14 g/m².

Ten layers of this composite material was circumferentially wrapped ontop of the covered mandrel, and tacked with a soldering iron. One layerof film consisting of only the above described fluoroelastomer (0.04 mm)was then wrapped on top of the previously applied film and tacked with asoldering iron, thereby creating a leaflet frame covering. For thistacking operation, a 0.03 mm thick polyimide film (Kapton polyimide,2271K1, McMaster-Carr, Santa Fe Springs Calif.) was temporarily placedbetween the fluoroelastomer film and the iron to prevent thefluoroelastomer film from adhering to the iron.

The clean leaflet frame was then placed over the leaflet frame coveringon the mandrel from the small diameter side of the taper until it fitsnugly, with the base of the frame toward the small diameter portion ofthe taper, as shown in FIG. 5A.

The leaflet frame covering that extended beyond the base of the frametoward the small taper was then everted over the frame until the entireframe was encapsulated and the folded edge of the everted material wasflush with the base of the frame to create an outer leaflet framecovering, as shown in FIG. 5B.

Approximately ten layers of a sacrificial longitudinally expanded PTFEfilm having a thickness of about 0.1 mm were tightly wrapped around thecovered frame. The resulting assembly was then placed in a convectionoven set at 320° C. for 20 minutes. This assembly was removed from theoven and allowed to cool, and the outer sacrificial layers were removed.This assembly was then removed from the mandrel, ensuring that it wasreleased from the inner sacrificial layer.

Using a surgical blade, the leaflet frame cover was trimmed, as shown inFIG. 2B, to create a construct 154 consisting of a leaflet frame 130, aleaflet reinforcing member 149 adjacent to one side of each post and astrain relief frame covering 152. The remainder of the frame coveringwas trimmed at 1 mm from the edge of the frame, leaving 6 mm leafletreinforcing member 149 on one side of each post, as shown in FIG. 5C,the leaflet window first side 133 a, as shown in FIG. 2A.

A leaflet material was then prepared having a membrane layer of ePTFEimbibed with a fluoroelastomer. More specifically, the membrane layer ofePTFE was manufactured according to the general teachings described inU.S. Pat. No. 7,306,729. The ePTFE membrane was tested in accordancewith the methods described below. The ePTFE membrane had a mass per areaof about 0.6 g/m², a porosity of about 90%, a thickness of about 3 μm, abubble point of about 450 KPa, a matrix tensile strength of about 350MPa in the longitudinal direction and about 250 MPa in the transversedirection. This membrane was imbibed with the same fluoroelastomer asdescribed above. The fluoroelastomer was dissolved in Novec HFE7500 (3M,St Paul, Minn., USA) in an about 2.5% concentration. The solution wascoated using a mayer bar onto the ePTFE membrane (while being supportedby a polypropylene release film) and dried in a convection oven set toabout 145° C. for about 30 seconds. After two coating steps, theresulting composite material of ePTFE/fluoroelastomer had a mass perarea of about 4 g/m².

The final leaflet was comprised of about 30% fluoropolymer by weightwith a thickness of 25 μm. Each leaflet had 31 layers of the composite.

The encapsulated frame with frame covering defining a strain relief anda reinforcing member was then attached to the leaflet material in acylindrical or tubular shape in the following manner. The encapsulatedframe with strain relief covering and reinforcing member was placed onthe release liner-covered tapered mandrel described above, as shown inFIG. 5D.

Thirty-one layers of the above described leaflet material werecircumferentially wrapped over the encapsulated frame, as shown in FIG.5D.

Approximately ten layers of a sacrificial longitudinally expanded PTFEfilm having a thickness of about 0.1 mm were tightly wrapped around thecovered frame. The resulting assembly was then placed in a convectionoven set at 280° C. for 60 minutes. This assembly was removed from theoven and allowed to cool, and the outer sacrificial layers were removed.This assembly was then removed from the mandrel, ensuring that it wasreleased from the inner sacrificial layer.

The leaflet material was trimmed approximately 5 mm above the leafletframe first end 121 a, also referred to as the frame top. The resultingassembly was placed in a convection oven set at 150° C. for 15 min whileclosing the valve with 5 cm of Hg vacuum to close the leaflets. Theassembly was removed from the oven and allowed to cool. Leaflets weretrimmed using scissors to a height of approximately 1-2 mm above thecoaptation line.

The average maximum leaflet thickness in the leaflet first side regionwas 281 micrometers and the average maximum leaflet thickness in theleaflet second side region was 27 micrometers. These measurements werean average of three measurements obtained on a Mitutoyo Litematic VL-50A(Aurora, Ill.) digimatic measuring unit.

The performance of the valve leaflets was characterized on a real-timepulse duplicator. The following results were obtained: EOA=1.9 cm² andregurgitant fraction=2.5%.

A geometric orifice area (GOA) test was performed. With a flow of 450ml/s of 37° C. saline flowing through the 22 mm ID valve, a picture wastaken of the leaflets in the fully open position. This image wasanalyzed by pasting the image in CAD software (SOLIDWORKS 2012). Acircle was drawn connecting the inner surface of the centers of each ofthe three posts. From the middle of each of these three posts, adiameter line was drawn. These diameter lines split the image into six(6) slices, or two slices per leaflet, similar to FIG. 1C. A spline line156 was then drawn around the full circumference of the edge of the openleaflets. The geometric orifice area (GOA) for each of the threeleaflets was then calculated by calculating the luminal area within thespline for the ⅓ of the total valve area encompassed by each leaflet.This resulted in a calculation of GOA for each leaflet (the sum of thesethree GOAs equals the GOA of the entire valve). Subsequently, the GOA ofeach side of the leaflet was calculated by using the diameter line drawnpreviously which bisects the leaflet. The GOA from the reinforcedsection of the leaflet is always less than the GOA of the unreinforcedsection. For the example presented above, the ratio of the GOA on thereinforced side of the leaflet to the total leaflet GOA was 34%, 37%,and 33%, while the other side of the leaflet had a ratio of 66%, 63%,and 67%, respectively.

Test Methods

Pulsatile Flow Testing

The flow performance was characterized by the following process:

The valve assembly was placed within a silicone annular ring (supportstructure), supporting its outer diameter without changing its diameter,to allow the valve assembly to be subsequently evaluated in a real-timepulse duplicator. The process was performed according to therecommendations of the pulse duplicator manufacturer (ViVitroLaboratories Inc., Victoria BC, Canada).

The valve assembly was then placed into a real-time left heart flowpulse duplicator system. The flow pulse duplicator system included thefollowing components supplied by ViVitro Laboratories Inc., Victoria BC,Canada: a Super Pump, Servo Power Amplifier Part Number SPA 3891; aSuper Pump Head, Part Number SPH 5891B, 38 cm² cylinder area; a valvestation/fixture; Vivitro software capable of waveform control and datacollection; I/O module Part Number XXXX, TriPack Part Number TP 2001; aSensor Interface, Part Number VB 2004; a Sensor Amplifier Component,Part Number AM 9991; and a Square Wave Electro Magnetic Flow Meter(positioned approximately 2 cm upstream of the valve), Carolina MedicalElectronics Inc., East Bend, N.C., USA. The outflow chamber used toevaluate the performance of the pulmonary valve was chosen such that theinternal diameter of the outflow chamber was matched to that of thevalve diameter. A 40 ml source compliance, a large peripheral compliancewas added to the tester to simulate physiological pulmonary conditions.Additionally, as a straight outflow chamber was used, the rootcompliance was not used in the test set-up.

In general, the flow pulse duplicator system uses a fixed displacement,piston pump to produce a desired fluid flow through the valve undertest. Testing and definitions are consistent with ISO 5840-3, 2013except where otherwise noted for testing to pulmonary conditions. Whilethis testing is conducted to pulmonary conditions, testing and use (e.g.aortic, mitral, tricuspid, venous, etc.) in other conditions is notexcluded.

The heart flow pulse duplicator system was adjusted to produce thedesired flow (5.0±0.5 L/min), mean pressure (20±2 mmHg), simulated pulserate (70 bpm), a 35% systolic duration sinusoidal waveform, and a strokevolume (i.e., the amount of fluid pushed by the driving pump) of 84±1ml. The operating temperature was 37±1° C. using 0.9% saline as testsolution. The valve under test was then cycled for between 5 to 15minutes.

Pressure and flow data were measured and collected during the testperiod for ten (10) continuous cardiac cycles, including rightventricular pressures, pulmonary pressures, flow rates, and pump pistonposition. Parameters used to characterize the valve are effectiveorifice area and regurgitant fraction. The effective orifice area (EOA),which can be calculated as follows: EOA (cm²)=Q_(rms)/(51.6*(ΔP)^(1/2))where Q_(rms) is the root mean square of the flow rate (cm³/s) duringthe positive pressure interval of systolic period and AP is the meandifferential pressure during the positive pressure interval of thesystolic period (mmHg) (note that density of saline is taken to be 1g/cm³, therefore this equation eliminates the density as compared to theequation presented in ISO 5840).

During this test, during the period when the maximum flow is flowingthrough the valve, a digital picture was taken. This picture was takenfrom the outflow region with the lens normal to the direction of flowwith a field of view to encompass the full outflow side of the valve.The flow rate was recorded from the Pulse Duplicator at this time andthe image used for GOA (Geometric Orifice Area) calculations.

Another measure of the hydrodynamic performance of a valve is theregurgitant fraction, which is the amount of fluid or blood regurgitatedthrough the valve divided by the Forward Volume (i.e., amount of flowpassing through the valve during the forward phase of the valve).

Steady Flow Testing

To demonstrate the asymmetrical opening of the leaflets in a steady flowapparatus, saline heated to 37° C. was pumped at a steady rate thoughthe valve to open it. Saline was pumped using a pump (WEG Electric,Duluth, Ga., part number 10086261) with voltage regulator (Staco EnergyProducts, Miamisburg, Ohio, part number 3PN2210B) though the valve at 5L/min (as measured by a large graduated cylinder and stopwatch). Thevalve was placed within a silicone holder in the recirculating loop thatstarted and finished within an open 37±1° C. heated reservoir. An imageof the valve was taken using a digital camera (Vision Research, Wayne,N.J., Model Miro EX4), and the GOA measured using the same technique asnoted previously. For all three leaflets, the geometric open area on onehalf of each leaflet was 39% of each leaflets total GOA (i.e. other halfof leaflet geometric open area was 61% of each leaflets total GOA).

Material Characterization Testing

As used in this application, the surface area per unit mass, expressedin units of m²/g, was measured using the Brunauer-Emmett-Teller (BET)method on a Coulter SA3100Gas Adsorption Analyzer, Beckman Coulter Inc.Fullerton Calif., USA. To perform the measurement, a sample was cut fromthe center of the expanded fluoropolymer membrane and placed into asmall sample tube. The mass of the sample was approximately 0.1 to 0.2g. The tube was placed into the Coulter SA-Prep Surface Area Outgasser(Model SA-Prep, P/n 5102014) from Beckman Coulter, Fullerton Calif., USAand purged at about 110° C. for about two hours with helium. The sampletube was then removed from the SA-Prep Outgasser and weighed. The sampletube was then placed into the SA3100 Gas adsorption Analyzer and the BETsurface area analysis was run in accordance with the instrumentinstructions using helium to calculate the free space and nitrogen asthe adsorbate gas.

Bubble point and mean flow pore size were measured according to thegeneral teachings of ASTM F31 6-03 using a capillary flow Porometer,Model CFP 1500AEXL from Porous Materials, Inc., Ithaca N.Y., USA. Thesample membrane was placed into the sample chamber and wet with SilWickSilicone Fluid (available from Porous Materials Inc.) having a surfacetension of about 20.1 dynes/cm. The bottom clamp of the sample chamberhad an about 2.54 cm diameter hole. Isopropyl alcohol was used as thetest fluid. Using the Capwin software version 7.73.012 the followingparameters were set as specified in the table below. As used herein,mean flow pore size and pore size are used interchangeably.

Parameter Set Point Maxflow (cm³/m) 200000 Bublflow (cm³/m) 100 F/PT(old bubltime) 50 Minbpress (PSI) 0 Zerotime (sec) 1 V2incr (cts) 10Preginc (cts) 1 Pulse delay(sec) 2 Maxpre (PSI) 500 Pulse width (sec)0.2 Mineqtime (sec) 30 Presslew (cts) 10 Flowslew (cts) 50 Eqiter 3Aveiter 20 Maxpdif (PSI) 0.1 Maxfdif (PSI) 50 Sartp (PSI) 1 Sartf(cm³/m) 500

Membrane thickness was measured by placing the membrane between the twoplates of a Käfer FZ1000/30 thickness snap gauge Käfer MessuhrenfabrikGmbH, Villingen-Schwenningen, Germany. The average of the threemeasurements was reported.

The presence of elastomer within the pores can be determined by severalmethods known to those having ordinary skill in the art, such as surfaceand/or cross section visual, or other analyses. These analyses can beperformed prior to and after the removal of elastomer from the leaflet.

Membrane samples were die cut to form rectangular sections about 2.54 cmby about 15.24 cm to measure the weight (using a Mettler-Toledoanalytical balance model AG204) and thickness (using a Käfer Fz1000/30snap gauge). Using these data, density was calculated with the followingformula: ρ=m/w*l*t, in which: ρ=density (g/cm³): m=mass (g), w=width(cm), l=length (cm), and t=thickness (cm. The average of threemeasurements was reported.

Tensile break load was measured using an INSTRON 122 tensile testmachine equipped with flat-faced grips and a 0.445 kN load cell. Thegauge length was about 5.08 cm and the cross-head speed was about 50.8cm/min. The sample dimensions were about 2.54 cm by about 15.24 cm. Forlongitudinal measurements, the longer dimension of the sample wasoriented in the highest strength direction. For the orthogonal MTSmeasurements, the larger dimension of the sample was orientedperpendicular to the highest strength direction. Each sample was weighedusing a Mettler Toledo Scale Model AG204, then the thickness measuredusing the Käfer FZ1000/30 snap gauge. The samples were then testedindividually on the tensile tester. Three different sections of eachsample were measured. The average of the three maximum loads (i.e., peakforce) measurements was reported. The longitudinal and transverse matrixtensile strengths (MTS) were calculated using the following equation:MTS=(maximum load/cross-section area)*(bulk density of PTFE)/(density ofthe porous membrane), wherein the bulk density of the PTFE was taken tobe about 2.2 g/cm³. Bending stiffness was measured by following thegeneral procedures set forth in ASTM D790. Unless large test specimensare available, the test specimen must be scaled down. The testconditions were as follows. The leaflet specimens were measured on athree-point bending test apparatus employing sharp posts placedhorizontally about 5.08 mm from one another. An about 1.34 mm diametersteel bar weighing about 80 mg was used to cause deflection in the y(downward) direction, and the specimens were not restrained in the xdirection. The steel bar was slowly placed on the center point of themembrane specimen. After waiting about 5 minutes, they deflection wasmeasured. Deflection of elastic beams supported as above can berepresented by: d=F*L³/48*EI, where F (in Newtons) is the load appliedat the center of the beam length, L (meters), so L=½ distance betweensuspending posts, and EI is the bending stiffness (Nm). From thisrelationship the value of EI can be calculated. For a rectangularcross-section: I=t³*w/12, where I=cross-sectional moment of inertia,t=specimen thickness (meters), w=specimen width (meters). With thisrelationship, the average modulus of elasticity over the measured rangeof bending deflection can be calculated.

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the present embodimentswithout departing from the spirit or scope of the embodiments. Thus, itis intended that the present embodiments cover the modifications andvariations of this invention provided they come within the scope of theappended claims and their equivalents.

What is claimed:
 1. A prosthetic valve comprising: a plurality ofleaflets, each leaflet including a leaflet first side region and aleaflet second side region opposite from the leaflet first side region,at least a first portion of the leaflet first side region having a firstthickness and the second side region having a second thickness, thefirst thickness is greater than the second thickness.
 2. The prostheticvalve of claim 1, wherein when in an open position, the leaflet firstside region contributes to a smaller geometric orifice area as comparedwith the leaflet second side region.
 3. The prosthetic valve of claim 2,wherein the leaflet second side region opens further than the leafletfirst side region during forward flow of up to 350 ml/sec.
 4. Theprosthetic valve of claim 2 wherein when in the open position, theleaflet first side region contributes up to a 70 percent smallergeometric orifice area as compared with the leaflet second side region.5. The prosthetic valve of claim 1, wherein the leaflet first sideregion has a first bending stiffness and the leaflet second side regionhas a second bending stiffness, the first bending stiffness beinggreater than the second bending stiffness.
 6. The prosthetic valve ofclaim 1, wherein the leaflet comprises at least one layer of a compositematerial, at least the first portion of the first side region comprisesmore layers of composite material than the second side region.
 7. Theprosthetic valve of claim 6, wherein the first thickness is up to tentimes greater than the second thickness of the leaflet second sideregion.
 8. The prosthetic valve of claim 7, wherein the first thicknessis at least 280 micrometer and the second thickness is 25 micrometer orgreater.
 9. The prosthetic valve of claim 1, wherein the first thicknessis greater than 110% of a second thickness.
 10. The prosthetic valve ofclaim 6 wherein at least the first portion of the leaflet first sideregion further comprises a leaflet reinforcing member, the leafletreinforcing member being operable to provide the first portion of theleaflet first side region with a first bending stiffness that is greaterthan a second bending stiffness of the leaflet second side region. 11.The prosthetic valve of claim 10, wherein the leaflet reinforcing membercomprises at least one layer of composite material coupled to at leastthe first portion of the leaflet first side region.
 12. The prostheticvalve of claim 1, wherein the leaflet comprises a polymeric material.13. The prosthetic valve of claim 1, further comprising: a leaflet framehaving a generally tubular shape, the leaflet frame defining a pluralityof leaflet windows wherein each of the leaflet windows includes aleaflet window first side, a leaflet window second side opposite theleaflet window first side, a leaflet window base therebetween, wherein aleaflet window side of one leaflet window is interconnected with aleaflet window side of an adjacent leaflet window, wherein the pluralityof leaflets being coupled to the leaflet frame, each leaflet including afree edge, a base opposite from the free edge and coupled to the leafletwindow base, and a leaflet central region between the leaflet first sideregion and the leaflet second side region, the leaflet first side regionbeing coupled to the leaflet window first side and the leaflet secondside region being coupled to the leaflet window second side.
 14. Theprosthetic valve of claim 13, wherein two adjacent leaflet window firstside and leaflet window second side terminates at a commissure post, theleaflet first side region being coupled to the leaflet window firstside, the leaflet second side region being coupled to the leaflet windowsecond side and the leaflet central region being coupled to the leafletwindow base.
 15. The prosthetic valve of claim 13, each leafletincluding a free edge, a base opposite from the free edge and coupled tothe leaflet window base, wherein the leaflet reinforcing member extendsto the free edge of the leaflet.
 16. The prosthetic valve of claim 1,further comprising: a leaflet frame having a generally tubular shape,the leaflet frame defining a plurality of leaflet windows wherein eachof the leaflet windows includes a leaflet window first side and aleaflet window second side opposite the leaflet window first side andcoupled thereto, wherein a leaflet window side of one leaflet window isinterconnected with a leaflet window side of an adjacent leaflet window;and a leaflet reinforcing member coupled to the leaflet window firstside, wherein the plurality of leaflets are coupled to the leafletframe, each leaflet including a free edge extending across the leafletwindow first side and a leaflet window second side, wherein the leafletfirst side region is coupled to the leaflet reinforcing member makingthe leaflet first side region stiffer than the leaflet second sideregion.
 17. The prosthetic valve of claim 16, wherein two adjacentleaflet window first side and leaflet window second side terminates at acommissure post, the leaflet first side region being coupled to theleaflet window first side, the leaflet second side region being coupledto the leaflet window second side.
 18. The prosthetic valve of claim 17,further comprising a vertical element extending from each of thecommissure posts.
 19. The prosthetic valve of claim 16, wherein theleaflet frame defines three interconnected leaflet windows having asubstantially trapezoidal shape.
 20. The prosthetic valve of claim 1,wherein the leaflet comprises a polymeric material.
 21. The prostheticvalve of claim 20, wherein the leaflet comprises a laminate.
 22. Theprosthetic valve of claim 21, wherein the laminate has more than onelayer of a fluoropolymer membrane.
 23. The prosthetic valve of claim 20,wherein the leaflet comprises a film having at least one fluoropolymermembrane having a plurality of pores and an elastomer present insubstantially all of the pores of the at least one fluoropolymermembrane.
 24. The prosthetic valve of claim 23, wherein the filmcomprises less than about 80% fluoropolymer membrane by weight.
 25. Theprosthetic valve of claim 23, wherein the elastomer comprises(per)fluoroalkylvinylethers (PAVE).
 26. The prosthetic valve of claim23, wherein the elastomer comprises a copolymer of tetrafluoroethyleneand perfluoromethyl vinyl ether.
 27. The prosthetic valve of claim 23,wherein the fluoropolymer membrane comprises ePTFE.
 28. A prostheticvalve comprising: a plurality of leaflets, each leaflet defines aleaflet first side region and a leaflet second side region opposite fromthe leaflet first side region, each leaflet defining a leaflet base anda leaflet free edge opposite from the leaflet base, each leaflet firstside region is coupled with the leaflet second side region of anadjacent leaflet at a commissure, the leaflet base of each of theplurality of leaflets together define an orifice, at least one of theleaflet second side regions extend further into the orifice than theleaflet first side region when the leaflets are in a fully openposition.
 29. The prosthetic valve of claim 28, wherein each of theleaflet first side regions extend further into the orifice than each ofthe leaflet second side regions when the leaflets are in the openposition.
 30. The prosthetic valve of claim 28, wherein each leafletincludes a leaflet first side region being defined by the leaflet firstside, each leaflet includes a leaflet second side region being definedby the leaflet second side.
 31. The prosthetic valve of claim 28,wherein when in the open position, the leaflet first side regioncontributes to a smaller geometric orifice area as compared with theleaflet second side region.
 32. The prosthetic valve of claim 31,wherein the leaflet second side region opens further than the leafletfirst side region during forward flow of up to 350 ml/sec.
 33. Theprosthetic valve of claim 31 wherein when in the open position, theleaflet first side region contributes up to a 70 percent smallergeometric orifice area as compared with the leaflet second side region.34. The prosthetic valve of claim 28, wherein the leaflet first sideregion has a first bending stiffness and the leaflet second side regionhas a second bending stiffness, the first bending stiffness beinggreater than the second bending stiffness.
 35. The prosthetic valve ofclaim 28, wherein the leaflet comprises at least one layer of acomposite material, at least a first portion of the first side regioncomprises more layers of composite material than the second side region.36. The prosthetic valve of claim 35, wherein the first portion of theleaflet first side region has a first thickness that is up to ten timesmore than a second thickness of the leaflet second side region.
 37. Theprosthetic valve of claim 36, wherein the first thickness is at least280 micrometer and the leaflet second side region has a second thicknessof 25 micrometer or greater.
 38. The prosthetic valve of claim 28,wherein a first thickness of the leaflet first side region is greaterthan 110% of a second thickness of the leaflet second side region. 39.The prosthetic valve of claim 35 wherein at least the first portion ofthe leaflet first side region further comprises a leaflet reinforcingmember, the leaflet reinforcing member being operable to provide thefirst portion of the leaflet first side region with a first bendingstiffness that is greater than a second bending stiffness of the leafletsecond side region.
 40. The prosthetic valve of claim 39, wherein theleaflet reinforcing member comprises at least one layer of compositematerial coupled to at least the first portion of the leaflet first sideregion.
 41. The prosthetic valve of claim 28, wherein the leafletcomprises a polymeric material.
 42. The prosthetic valve of claim 28,further comprising: a leaflet frame having a generally tubular shape,the leaflet frame defining a plurality of leaflet windows wherein eachof the leaflet windows includes a leaflet window first side, a leafletwindow second side opposite the leaflet window first side, a leafletwindow base therebetween, wherein a leaflet window side of one leafletwindow is interconnected with a leaflet window side of an adjacentleaflet window, wherein the plurality of leaflets being coupled to theleaflet frame, each leaflet including a free edge, a base opposite fromthe free edge and coupled to the leaflet window base, and a leafletcentral region between the leaflet first side region and the leafletsecond side region, the leaflet first side region being coupled to theleaflet window first side and the leaflet second side region beingcoupled to the leaflet window second side.
 43. The prosthetic valve ofclaim 42, wherein two adjacent leaflet window first side and leafletwindow second side terminates at a commissure post, the leaflet firstside region being coupled to the leaflet window first side, the leafletsecond side region being coupled to the leaflet window second side andthe leaflet central region being coupled to the leaflet window base. 44.The prosthetic valve of claim 41, wherein the leaflet reinforcing memberextends to the free edge of the leaflet.
 45. The prosthetic valve ofclaim 28, further comprising: a leaflet frame having a generally tubularshape, the leaflet frame defining a plurality of leaflet windows whereineach of the leaflet windows includes a leaflet window first side and aleaflet window second side opposite the leaflet window first side andcoupled thereto, wherein a leaflet window side of one leaflet window isinterconnected with a leaflet window side of an adjacent leaflet window;and a leaflet reinforcing member coupled to the leaflet window firstside, wherein the plurality of leaflets are coupled to the leafletframe, each leaflet including a free edge extending across the leafletwindow first side and a leaflet window second side, wherein the leafletfirst side region is coupled to the leaflet reinforcing member makingthe leaflet first side region stiffer than the leaflet second sideregion.
 46. The prosthetic valve of claim 45, wherein two adjacentleaflet window first side and leaflet window second side terminates at acommissure post, the leaflet first side region being coupled to theleaflet window first side, the leaflet second side region being coupledto the leaflet window second side.
 47. The prosthetic valve of claim 46,further comprising a vertical element extending from each of thecommissure posts.
 48. The prosthetic valve of claim 45, wherein theleaflet frame defines three interconnected leaflet windows having asubstantially trapezoidal shape.
 49. The prosthetic valve of claim 45,wherein the leaflet comprises a polymeric material.
 50. The prostheticvalve of claim 49, wherein the leaflet comprises a laminate.
 51. Theprosthetic valve of claim 50, wherein the laminate has more than onelayer of a fluoropolymer membrane.
 52. The prosthetic valve of claim 49,wherein the leaflet comprises a film having at least one fluoropolymermembrane having a plurality of pores and an elastomer present insubstantially all of the pores of the at least one fluoropolymermembrane.
 53. The prosthetic valve of claim 52, wherein the filmcomprises less than about 80% fluoropolymer membrane by weight.
 54. Theprosthetic valve of claim 52, wherein the elastomer comprises(per)fluoroalkylvinylethers (PAVE).
 55. The prosthetic valve of claim52, wherein the elastomer comprises a copolymer of tetrafluoroethyleneand perfluoromethyl vinyl ether.
 56. The prosthetic valve of claim 52,wherein the fluoropolymer membrane comprises ePTFE.
 57. A method offorming a prosthetic valve, comprising: providing a leaflet frame havinga generally tubular shape, the leaflet frame defining a frame outersurface and a plurality of leaflet windows wherein each of the leafletwindows includes a leaflet window first side, a leaflet window secondside opposite from the leaflet window first side, a leaflet window base,and a leaflet window top; providing a film; providing a mandrel;wrapping a first film layer into a tubular form about the mandrel;placing the leaflet frame over the first film layer; everting the firstfilm over the frame to cover the frame outer surface defining anassembly; thermally setting the assembly; trimming the first film layerto define a leaflet reinforcing member that is at least a portion of aleaflet first side region adjacent to and depending from the leafletwindow first side and removing the first film layer from the leafletwindow that substantially defines a leaflet central region and a leafletsecond side region; trimming the first film layer to within about 0.5 to1.0 mm of the leaflet window second side within the leaflet window;define at least a portion of the leaflet first side region and removingthe first film layer from the leaflet window that substantially definesthe leaflet second side region; forming a second film layer over theleaflet frame; thermally setting the assembly; receiving the assemblyover a mandrel; and cutting the film across the leaflet window topwithin the leaflet window.
 58. The method of forming a prosthetic valveof claim 57, wherein wrapping the film about the leaflet frame compriseswrapping a second film about an inner surface of the leaflet frame and athird film about an outer surface of the leaflet frame, wherein theleaflets are defined by the second film and the third film coupledtogether in the leaflet windows.